The Hallmarks of a Cancer Discovery
Authors: Luis A. Diaz, Lewis C. Cantley
Journal: Cancer Discovery (2023)

A strength of Cancer Discovery since its launch has been its pioneering mix of studies providing fundamental insights into cancer biology alongside the preclinical development of novel agents, "bedside to bench" translational studies, and clinical trials that have collectively had an immediate impact on our understanding of cancer and guided advances in treatment. The central mission of the journal is to bring together a broad spectrum of cancer researchers and clinicians to catalyze a discussion of the most impactful and innovative science across all areas of cancer biology.This community conversation is fueled by each new study that the journal publishes and so we are often asked, what makes a finding worthy of Cancer Discovery?At the outset, Cancer Discovery provided a much-needed home for translational research manuscripts. The journal has featured many meaningful studies on the preclinical characterization and proof-of-concept clinical efficacy of emerging targeted and immune therapies, several of which have resulted in subsequent clinical breakthroughs and FDA approvals. For example, preclinical studies published in Cancer Discovery paved the way for the recent development of KRASG12C inhibitors and have shown the promise of new therapeutic agents, such as those targeting p53 and KRASG12D and novel immunotherapy approaches. In addition, numerous Cancer Discovery articles have provided crucial insights into mechanisms of therapeutic resistance in the clinic or have tested potential strategies to delay resistance and improve efficacy through combination therapies.From its earliest issues, Cancer Discovery has also published clinical trials that build on these translational studies, leading to practice-changing advances that benefit patients. For instance, the BATTLE trial (1), published in the very first issue of the journal in 2011, was at the vanguard of personalized cancer medicine. Since then, Cancer Discovery has been dedicated to advancing precision medicine and genome-driven therapy trials. In addition, the journal has a strong track record in publishing reports of early-phase trials that are hypothesis-driven and feature strong biomarker or scientific correlate analyses. Clinical studies assessing potential biomarkers of response and combinatorial therapeutic strategies are key to achieving an understanding of mechanisms of action and to further improve efficacy and patient selection.Cancer Discovery is equally inspired by fundamental insights into cancer biology. We recognize the essential importance of basic science, which forms the foundation for translational and clinical studies. Studies in model organisms and cancer cell lines are of indispensable value in uncovering new functional insights and molecular mechanisms, and clinical samples or therapeutic interventions are not necessarily needed to change the way we think about cancer. We continue to encourage the submission of hypothesis-driven studies that report compelling biological discoveries or mechanistic insights that increase our understanding of cancer.In recent years, we have witnessed an increased emphasis on translational and clinical research in high-impact journals—to some extent at the expense of fundamental biology. Although some journals may continue to focus more exclusively on clinical and translational content, Cancer Discovery is committed to publishing the entire spectrum of research. In doing so, our goal is not only to expand our knowledge of cancer biology but also to reveal new questions, with the ultimate goal of improving patient care.Emblematic of Cancer Discovery's dedication to understanding the very nature of cancer itself is our presentation of "Hallmarks of Cancer: New Dimensions" (2), characterizing an additional four Cancer Hallmarks and emphasizing the cooperative role of various basic biological and cellular processes in tumor initiation and progression. Research that more fully defines the underlying mechanisms and molecular drivers by which these newest hallmarks—phenotypic plasticity, nonmutational epigenetic reprogramming, polymorphic microbiomes, and senescent cells—promote tumorigenesis will be necessary to move the field forward and develop novel therapeutic strategies.We strive to be the journal showcasing emerging or yet-to-be-defined hallmarks and are dedicated to expanding into new and growing research areas to push past the limits of our knowledge of cancer biology. This includes studies harnessing the latest technological advances, such as single-cell spatial technologies and artificial intelligence, that provide unprecedented insights into resistance mechanisms, cancer evolution, or early detection.As we move forward, Cancer Discovery is committed to driving awareness of cancer disparities and leading discussions of oncology in a global context to transform cancer therapies and improve outcomes for all patients around the world. The journal seeks to work with the community to disseminate findings addressing the biggest unanswered questions in the field—for example, in this issue, we share with readers the latest Cancer Grand Challenges identified after a global consultation with cancer researchers, patients, and others affected by cancer (3). Solving long-standing problems such as these will require engagement and innovative thinking from the international cancer research community and will call upon the full spectrum of our scope—from mechanism to translation to clinic.If you are inspired by the journal's mission, we want to go forward together. If you have timely ideas, we want to amplify your voice. If you have an exciting cancer discovery, we want to hear from you.L.A. Diaz is a member of the board of directors of Jounce Therapeutics; a compensated consultant for PetDx, Innovatus CP, Se'er, Delfi, Kinnate, and Neophore; and an uncompensated consultant for Merck but has received clinical trial support from Merck. He is an inventor of multiple licensed patents related to technology for circulating tumor DNA analyses and mismatch repair deficiency for diagnosis and therapy from Johns Hopkins University; some of these licenses and relationships are associated with equity or royalty payments directly to him and Johns Hopkins. He holds equity in Jounce Therapeutics, PetDx, Se'er, Delfi, Kinnate, and Neophore. He divested his equity in Personal Genome Diagnostics to LabCorp in February 2022 and divested his equity in Thrive Earlier Detection to Exact Biosciences in January 2021. His spouse holds equity in Amgen. The terms of all these arrangements are being managed by Johns Hopkins and Memorial Sloan Kettering in accordance with their conflict of interest policies. L.C. Cantley reports a grant from the NCI (R35 CA197588) during the conduct of the study.